Heart Failure
Chronic heart failure results from a variety of insults to the cardiac tissues. In early disease ventricular contractility is largely maintained by adrenergic stimulation. As disease progresses compensatory mechanisms cease to provide benefit, fibrosis and dilation occur and function deteriorates. Left ventricular assist devices allow the left ventricle to repair and recover. We demonstrated a number of these repair outcomes, such as restored membrane integrity, improved calcium handling, and better mechnical indices. One major problem associated with heart failure is the ability of the myocytes to control calcium concentrations, indicating the vital role of adrenoreceptors. However, these receptors are down regulated and desensitized, possibly as a a protective mechanism against ionic overload, but our findings have indicated a) that the receptors are up-regulated during unloading, and regain normal numbers and sensitivity; b) that both alpha and beta adrenoreceptors are involved in recovery; and c) there is a mechanism in place to bring about a homogeneous distribution of the adrenoreceptors.
Our future studies will investigate changes in receptor subtypes to delineate specific receptors and their involvement and relocalization in this recovery process. We also wish to take our formulated data and correlate these changes with patient outcome, type of LVAD used, and pre-LVAD treatment (use of beta-blockers and/or intra aortic ballon for example). The ultimate aim is to use the types and numbers of receptors at the time of LVAD implantation to dictate something of a predictive factor as to probable outcome and the best treatment protocols. If this can be achieved, and we have had some success with 'blind' predictions of prior LVAD recipients, then there is every chance that another weapon can be added to the arsenal for treating heart failure, and deciding the likelihood of progression to organ transplantation with appropriate drug regimens, continued use of LVAD support, or an immediate need for tranplant surgery.
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Cardiac Muscle
Brian Poindexter, Roger Bick, Green shows cardiac actin
Sub-endocardial purkinje fibers
Brian Poindexter, Roger Bick, Sub-endocardial purkinje fibers of human myocardium. Red probe identifies dystrophin.
De-differentiating myocyte
Brian Poindexter, David Sheikh-Hamad, Michael Stephen, Roger Bick, Dedifferentiating, binucleate (white) cultured adult cardiomyocyte. Red demonstrates perinuclear stanniocalcin-1 synthesis.
Cardiac dystrophin
Roger Bick, OH Frazier (Texas Heart Institute), Brian Poindexter, Disrupted, cardiac dystrophin (green) surrounding myofibrils (red) from a core sample of a heart failure patient.
α adrenoreceptors
Pippa Evans, Brian Poindexter, OH Frazier, Roger Bick, Red alpha-adrenoreceptors on green myofibrils of a core sample prior to LVAD implantation. Reference - Schnee, PM et al, J Heart Lung Transpl. 27(7):710-717, 2008.
α adrenoreceptors
Pippa Evans, Brian Poindexter, OH Frazier, Roger Bick, Red alpha-adrenoreceptors on green myofibrils of a core sample prior to LVAD implantation. Reference - Schnee, PM et al, J Heart Lung Transpl. 27(7):710-717, 2008.
Beating myocytes
Brian Poindexter, Roger Bick, High nuclear calcium (white) seen in cultured neonatal cardiomyocytes.
Binucleated cardiomyocyte
Michael Stephen (UT-Cardiology), Roger Bick, Johan Moolman (Univ. of Stellenbosch), David Sheikh-Hamad (BCM), Brian Poindexter,
3D model of multiple stacked images of a cardiac myocytes showing the binucleate (white) form, synthesized proteins (red) and blue cardiac actin.
Ca channel proteins (3D)
Brian Poindexter, Roger Bick,
L-type calcium channel proteins (red) in the nuclear envelope of a cardiomyocyte.
Ca in heart cell
Brain Poindexter, Roger Bick,
Fluo 3 probed calcium in beating heart adult rodent heart cells.
Reference - Poindexter BJ et al, Cell Calcium; 30(6):373-82, 2001.
Cardiomyocytes
Roger Bick, Brian Poindexter, Textured rendition of a cultured, binucleate cardiomyocyte
Cardiomyocytes
Roger Bick, OH Frazier, Brian Poindexter, Pippa Schnee, Beta-adrenoreceptors (yellow) distributed along cardiac myosin (red) prior to cardiac unloading by LVAD. Reference - Schnee, PM et al, Medscape General Medicine, http://www.medscape.com/viewarticle/530973_print, 8(2):45, 2006.
Cardiomyocytes
Roger Bick, OH Frazier, Brian Poindexter, Pippa Schnee, Alpha-adrenoreceptors (yellow) distributed along cardiac actin (green) prior to cardiac unloading by LVAD. Reference - Schnee, PM et al, Medscape General Medicine, http://www.medscape.com/viewarticle/530973_print, 8(2):45, 2006.
Cardiomyocytes
Roger Bick, OH Frazier, Brian Poindexter, Pippa Schnee,
Alpha-adrenoreceptors (red) distributed along cardiac actin (green) prior to cardiac unloading by LVAD and acquired images are stacked to give a 3D rendition.
Reference - Schnee, PM et al, Medscape General Medicine, http://www.medscape.com/viewarticle
/530973_print, 8(2):45, 2006.
Perinuclear adrenoreceptors
Brian Poindexter, Roger Bick, Perinuclear distribution model of alpha-adrenoreceptors (red) before cardiac unloading via LVAD.
Contractile sequence
Brian Poindexter, L. Max Buja, Roger Bick,
Adult cardiomyocyte acquisitions of real time fluorescence calcium transients.
Reference - Poindexter BJ et al, Cell Calcium; 30(6):373-82, 2001.
